Tamed fox shows domestication's effects on the brain

Gene activity changes accompany doglike behavior

COLD SPRING HARBOR, N.Y. – Taming foxes changes not only the animals’ behavior but also their brain chemistry, a new study shows.

The finding could shed light on how the foxes’ genetic cousins, wolves, morphed into man’s best friend. Lenore Pipes of Cornell University presented the results May 10 at the Biology of Genomes conference.

The foxes she worked with come from a long line started in 1959 when a Russian scientist named Dmitry Belyaev attempted to recreate dog domestication, but using foxes instead of wolves. He bred silver foxes (Vulpes vulpes), which are actually a type of red fox with white-tipped black fur. Belyaev and his colleagues selected the least aggressive animals they could find at local fox farms and bred them. Each generation, the scientists picked the tamest animals to mate, creating ever friendlier foxes. Now, more than 50 years later, the foxes act like dogs, wagging their tails, jumping with excitement and leaping into the arms of caregivers for caresses.

At the same time, the scientists also bred the most aggressive foxes on the farms. The descendents of those foxes crouch, flatten their ears, growl, bare their teeth and lunge at people who approach their cages.

The foxes’ tame and aggressive behaviors are rooted in genetics, but scientists have not found DNA changes that account for the differences. Rather than search for changes in genes themselves, Pipes and her colleagues took an indirect approach, looking for differences in the activity of genes in the foxes’ brains.

The team collected two brain parts, the prefrontal cortex and amygdala, from a dozen aggressive foxes and a dozen tame ones. The prefrontal cortex, an area at the front of the brain, is involved in decision making and in controlling social behavior, among other tasks. The amygdala, a pair of almond-size regions on either side of the brain, helps process emotional information.

Pipes found that the activity of hundreds of genes in the two brain regions differed between the groups of affable and hostile foxes. For example, aggressive animals had increased activity of some genes for sensing dopamine. Pipes speculated that tame animals’ lower levels of dopamine sensors might make them less anxious.

The team had expected to find changes in many genes involved in serotonin signaling, a process targeted by some popular antidepressants such as Prozac. Tame foxes are known to have more serotonin in their brains. But only one gene for sensing serotonin had higher activity in the friendly animals.

In a different sort of analysis, Pipes discovered that all aggressive foxes carry one form of the GRM3 glutamate receptor gene, while a majority of the friendly foxes have a different variant of the gene. In people, genetic variants of GRM3 have been linked to schizophrenia, bipolar disorder and other mood disorders. Other genes involved in transmitting glutamate signals, which help regulate mood, had increased activity in tame foxes, Pipes said.

It is not clear whether similar brain chemical changes accompanied the transformation of wolves into dogs, said Adam Freedman, an evolutionary biologist at Harvard University. Even if dogs and wolves now have differing brain chemical levels, researchers can’t turn back time to watch the process unfold; they can only guess at how domestication happened. “We have to reconstruct an unobservable series of steps,” he said. Pipes’ study is an interesting example of what might have happened to dogs’ brains during domestication, he said.